During development, axons grow long distances in the central nervous system to contact their specific targets, while in the adult, there is little axon growth following a lesion and functional recovery is limited. Immature astrocytes have been proposed to be the cellular substrate for axon growth during development, and after a lesion to the adult CNS, "reactive" mature astrocytes are a major cellular component of glial scars that have been proposed to block axon growth. These observations suggest that the capacity of astrocytes to support and direct growth alters during CNS maturation. The molecular basis underlying the ability of astrocytes to support axon growth during development, and its modulation during astrocyte maturation is unknown. This study is designed to determine if changes in the interactions both between astrocytes and neurons; as well as between astrocytes and astrocytes, are responsible for the inhibition of neurite outgrowth by astrocytes after maturation. Dr. Miller will identify molecules involved in the following changes observed when astrocytes mature: (1) Neurite outgrowth is reduced on mature astrocytes, (2) Neurons have decreased adhesion to mature astrocytes, and (3) Astrocyte/astrocyte adhesion increases in mature astrocytes. In addition, neurite growth will be compared in a 3-dimensional matrix of immature or mature astrocytes, and the perturbation of cell interactions involving astrocyte/neuron and astrocyte/astrocyte adhesion in this system will be determined. These studies will provide new information on the regulation of axon outgrowth by astrocytes of the developing and adult CNS.
